The intestine depends on regulated expression of plasma membrane transport proteins to absorb fluid and electrolytes properly. Abnormalities in electrolyte transport form the common pathogenetic pathway of the majority of diarrheal illnesses, regardless of etiology. The subject of this study is the Na-independent Cl:HCO3 exchanger. The Cl:HCO3 exchange is essential for NaCI absorption, as well as for the regulation of intracellular pH and cell volume. The Cl:HCO3 exchanger extrude alkali and regulate intracellular pH (PHi), which is important for man cellular processes and participates in mitogenic response to growth factors. The other major function of the Cl:HCO3 exchanger is the regulation of cell volume. The intestine epithelial cells absorb the nutrients, solutes and drugs presented to its luminal surface, and therefore are particularly vulnerable to changes in osmolality, the principal determinant of cell volume. The Cl:HCO3 exchanger conducts regulatory volume changes to restor e volume homeostasis. The Physiologic role of the Cl:HCO3 exchanger differs according to the segment or cell type in the digestive tract. The molecular basis for regulating the expression the Cl:HCO3 exchanger is unknown. However it is known that the Cl:HCO3 exchanger in the intestine is encoded by the AE2 class of the Anion Exchanger (AE) gene family. We have identified an enterocyte C:HCO3 exchanger and demonstrated that it is an AE2. Our preliminary data indicate that AE2 transcript is regulated during development and provide evidence for transcriptional regulation of AE2. We hypothesize that AE2 is regulated during development and differention of the intestine, and that the differential expression of AE2 is responsible for the regional, cell type and age-related differences in the expression of the Cl:HCO3 exchanger. Our goal is tousle molecular techniques to identify the sequence elements in the AE2 gene and the molecular mechanisms that utilize these sequences to regulate the expression of AE2 Cl:HCO3 exchanger during development and differentiation of the intestine. The findings of this study should be applicable to the understandings of the pathogenesis of diarrheal illnesses, the ontogeny of the Cl:HCO3 exchanger, as well as how changes in pH or volume homeostasis relate to growth and differentiation of intestinal cells.